Itvisma Wins FDA Approval as Novartis’ Second SMA Gene Therapy

Novartis has won FDA approval for its gene therapy Itvisma (onasemnogene abeparvovec-brve, and also known as OAV101 IT) for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients two years of age and older who have a confirmed mutation in the survival motor neuron 1 (SMN1) gene.

The therapy is a new version of the company’s SMA gene therapy Zolgensma, which received FDA approval in 2019.

While both contain the same active ingredient, they differ in their formulation due to different routes of administration. While Itvisma is a direct intrathecal injection (into the cerebrospinal fluid) around the spinal cord, Zolgensma is administered intravenously.

Due to its formulation, Itvisma can be given independent of patient weight, and hence to both children and adults, whereas Zolgensma is restricted to patients two years of age and younger.

Because of Itvisma’s intrathecal route, the vector dose can be lower and the delivery is more direct to the central nervous system/motor neuron target.

Related: FDA Places New Restrictions on Sarepta’s Elevidys Gene Therapy After DMD Patient Deaths

Both therapies are adeno-associated virus (AAV) vector-based that deliver a functional copy of the SMN1 gene into motor neurons, thereby restoring SMN protein production and halting (or greatly slowing) disease progression.

SMA is an autosomal recessive neurodegenerative disorder caused by mutations in the SMN1 gene. These mutations lead to progressive loss of motor neurons, muscle atrophy, weakness, paralysis and in the most severe cases, death.

The incidence is approximately four to 10 per 10,000 live births in the US prior to the availability of effective treatments. According to Novartis’ press release announcing the approval, around 9,000 individuals in the US live with SMA, with “unmet needs for older children, teens and adults in preserving motor neurons and maintaining physical strength.”

Historically, SMA has been one of the leading genetic causes of infant mortality.

“The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups,” said John W. Day, MD, PhD, professor of Neurology and Pediatrics, director, Division of Neuromuscular Medicine at Stanford University School of Medicine, and co-director of Stanford’s Neuro IGNITE Center.

“This achievement is not only a significant step forward for SMA — it also signals new possibilities for the broader field of neurological disorders and genetic medicine.”

As a one-time gene therapy, Itvisma is aimed at patients who may want to move away from the burden of chronic therapy. Novartis expects many candidates for the gene therapy to switch from existing treatments like Biogen’s Spinraza and Roche’s Evrysdi, noted a Novartis spokesperson.

Itvisma’s approval was based on data from the Phase III STEER study and supported by the open-label Phase IIIb STRENGTH study.

Itvisma showed statistically significant improvements in motor function and stabilization of motor abilities typically not seen in the natural history of the disease, with effects sustained over 52 weeks of follow-up.

In the STEER study, SMA patients aged two to under 18 years who received a single injection of Zolgensma into the spinal fluid experienced a 2.39-point gain on the Hammersmith Functional Motor Scale Expanded (HFMSE) motor function scale one year after treatment, compared to a 0.51-point improvement among patients who underwent a sham procedure.

“While the numbers might not look huge, what it means from a clinical impact to a patient is that they’re able to continue to use their wheelchair controls, or they’re able to continue to walk,” said Tracey Dawson, PhD, Novartis’ head of US neuroscience business, in an interview with Fierce Pharma.

She added that even seemingly small improvements, like maintaining grip strength, can make a significant difference for SMA patients.

Data from the studies were presented at the 2025 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference.

As with most gene therapies, Itvisma also has a steep price tag, coming in at $2.59 million.

A company spokesperson told Fierce Pharma that the one-time gene therapy is expected to cost 35% to 46% less over 10 years compared with currently available chronically dosed treatments.

With its broader eligible patient population, Novartis is projecting multibillion-dollar peak sales for Itvisma.

Zolgensma has been used to treat more than 5,000 patients worldwide since its 2019 approval, generating $1.2 billion in sales last year and securing its position as the world’s top-selling gene therapy.

Novartis is bolstering its neuromuscular ambitions with a roughly $12 billion bid for Avidity Biosciences. The deal brings an RNA-based antibody oligonucleotide conjugate platform and three late-stage muscular dystrophy programs.

Last year, the company picked up AAV muscular dystrophy gene therapy specialist Kate Therapeutics, which works on in vivo transgene RNA expression.

Novartis said Itvisma will be available in December this year.